The application proposes a population-based case-control study in men and women to examine the hypothesis that bladder cancer is caused by ingestion of arsenic in drinking water at lower concentrations than previously studied. The study population includes residents of Kings County in California and six counties in Nevada. These counties include water supplies containing close to 100 ug/litre of arsenic (the highest level of arsenic found in major water supplies in the U.S.). Other water supplies in the study region contain less than 10 ug/litre and thus provide a marked contrast in exposure. A total of 196 bladder cancer cases diagnosed in the study area between 1994 and 2000 will be identified from the California and Nevada Tumor Registries. Random digit dialing will be used to identify controls, frequency matched to cases by sex and 5 year age group in a 2:1 ratio. Controls over age 65 years will be supplemented as needed by random selection from the rolls of HCFA. Structured personal telephone interviews of the 1996 cases and 392 controls will be conducted by trained interviewers. The key interview questions will concern life-time residential history which will be linked to data on water arsenic concentrations. Questions will also be asked concerning typical volumes of water consumed in beverages and soups, both current at the time of interview and around 20 years prior to interview. Information will be obtained regarding cigarette smoking, which may be synergistic with arsenic in causing bladder cancer, chlorination of drinking water, diet, and occupational history. Analyses will be conducted using univariate and multivariate statistics with careful attention paid to potential confounders and to latency. The proposed study has over 90% statistical power to detect a relative risk of 2.0 which was predicted by linear extrapolation of data from studies in Taiwan. The study has scientific importance in seeking to identify whether exposure to arsenic at these levels actually increases bladder cancer risks, and public health importance because arsenic in water may pose one of the highest risks for cancer from environmental exposures.